Neutrophic factors are a potential candidate for treating neurodegenerative diseases such as Alzheimer's disease. A crucial step for advancing the clinical use of trophic factors will be the design of strategies for delivering these large molecules into the CNS over long periods of time. Gene therapy is a promising approach for accomplishing this task. The proposed work is aimed at expanding our knowledge concerning the impact of delivering trophic factors, particularly NGF, by gene therapy techniques into the primate CNS. Specifically, existing gene therapy approaches and established assays will be used for evaluating i) the distribution of NGF delivered within the primate CNS by gene therapy techniques, ii) the impact of ectopically delivered NGF upon NGF-sensitive basal forebrain cholinergic neurons in the unlesioned, young adult animal (both in terms of cell performance and normal target innervation), and iii) age-related changes in the response of basal forebrain cholinergic neurons to the actions of NGF delivered by gene therapy approaches (especially pertaining to the impact exogenous NGF will have upon normal target innervation).